The phase 1/2 X-Calibur trial is launching to explore 64Cu SAR-bisPSMA in patients with known or suspected prostate cancer, according to Clarity Pharmaceuticals, the manufacturer of the novel PSMA-PET imaging agent.1
The prospective, nonrandomized, single-arm, single-center, open-label X-Calibur study (NCT05286840) is being led by Luke Nordquist, MD, a urologic medical oncologist at the Urology Cancer Center and GU Research Network (GURN) in Omaha, Nebraska.
The study has a targeted enrollment of 150 patients with known or suspected prostate cancer. The investigators will be screening patients over a 28-day period to determine their eligibility. Patients meeting study inclusion criteria will be given a single administration of 64Cu SAR-bisPSMA, along with a PET scan at 1 to 4 hours and again at 24 to 72 hours.
The primary outcome measure of the study is safety. Secondary outcome measures include disease status adjustment, disease staging adjustment, and clinical management plan prior to and following 64Cu SAR-bisPSMA PET/CT Imaging. Another key outcome measure investigators will assess is the disease detection capability of this novel PSMA-PET imaging agent.
There are several other ongoing trials exploring 64Cu SAR-bisPSMA, including the phase 1/2 SECURE trial examining the novel PSMA theranostic 64/67Cu SAR-bisPSMA in patients with metastatic castration-resistant prostate cancer (mCRPC).2 The theranostic 64/67Cu SAR-bisPSMA combines 64Cu SAR-bisPSMA and the PSMA targeted therapy 67Cu SAR-bisPSMA.
In the open-label, single-arm, dose-escalation SECURE trial, 64Cu SAR-bisPSMA will be used for the selection of appropriate patients to receive treatment with 67Cu SAR-bis-PSMA. The study aims to enroll 44 patients at multiple locations in the United States.
To enroll on the trial, patients must have mCRPC that has progressed despite being treated with androgen-deprivation therapy and at least 1 second-generation androgen receptor pathway inhibitor, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi). Patients are required to have an ECOG performance status of 0 to 2, and a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). Individuals with brain metastases are not eligible to enroll.
"We are very impressed with the PET imaging data collected at GURN from the SECURE trial which indicates high tumor targeting and retention, especially compared to first-generation PSMA agents that use a single PSMA binding motif and have very short half-lives of 1-2 hours,” Nordquist stated in a press release. “As such, we were excited to seize the opportunity and continue the development of SAR-bisPSMA in the diagnostic investigator-initiated trial at GURN, continuing to further expand the clinical benefits of the product and to provide our own prostate cancer patients with the very best technologies available.”
Nordquist continued, "In addition to the clinical advantages, we have also been excited about the supply and logistical benefits of SAR-bisPSMA as a TCT, which can be distributed on-demand and in large scale from central manufacturing facilities. TCT can provide universal access to radiopharmaceuticals in every zip-code in the continental US, something that is lacking with current approved agents. GURN has a significant backlog of patients who cannot access sufficient quantities of PSMA imaging agents based on gallium-68 (Ga-68) or fluorine-18 (F-18) due to the logistical issues of short half-life isotopes. We have already experienced the benefits of Cu-64 based products and their longer shelf-life of up to 48 hours with our current trial with Clarity, and we expect minimal delays and interruptions as we look to address the large backlog of treatments, providing up to 150 prostate cancer patients with the critical imaging required to improve patient outcomes."
1. New clinical trial collaboration for Cu-64 SAR-bisPSMA in prostate cancer. Published online and accessed March 24, 2022. https://prn.to/382nxgw
2. NIH ClinicalTrials.gov. 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECURE). Last updated November 5, 2021. Accessed March 24, 2022. https://clinicaltrials.gov/ct2/show/NCT04868604